TITLE:
Role of α-Tubulin Acetylation and Protein Kinase D2 Ser/Tyr Phosphorylation in Modulation by Ghrelin of Porphyromonas gingivalis-Induced Enhancement in Matrix Metalloproteinase-9 (MMP-9) Secretion by Salivary Gland Cells
AUTHORS:
Bronislaw L. Slomiany, Amalia Slomiany
KEYWORDS:
Porphyromonas gingivalis, Oral Mucosa, Ghrelin, MMP-9, α-Tubulin Acetylation, Arf1, PKD2 Ser/Tyr Phosphorylation
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.4 No.7,
July
11,
2016
ABSTRACT: Matrix
metalloproteinas-9 (MMP-9) is a glycosylated endopeptidase, and hence its
processing between the endoplasmic reticulum (ER), Golgi and trans-Golgi (TGN)
network remains under a strict control of factors that affect the microtubule
(MT) stabilization, and the recruitment and activation of coat and cargo
proteins, including ADP-ribosylation factors (Arfs) and protein kinase D (PKD).
Here, we report on the factors implicated in the regulation of MMP-9 secretion
by salivary gland acinar cells in response to P. gingivalis LPS, and the effect of hormone, ghrelin. We show that
the LPS-elicited induction in MMP-9 secretion is associated with the increase
in α-tubulin acetylation and the
enhancement in MT stabilization, while the modulatory effect of ghrelin is
reflected in a decrease in α-tubulin
acetylation. Further, the effect of the LPS occurs in concert with up-regulation
in Arf-guanine nucleotide exchange factor (GEF)-mediated Arf1 activation and
the TGN recruitment of PKD2, while ghrelin exerts the modulatory effect on
Arf-GEF activation. Moreover, we reveal that the LPS-induced up-regulation in
MMP-9 secretion is reflected in a marked increase in PKCδ-mediated PKD2 phosphorylation on Ser, while the modulatory effect
of ghrelin is manifested by the SFK-PTKs-dependent phosphorylation of PKD2 on
Tyr. The findings demonstrate that MT stabilization along with Arf-GEF-mediated
Arf1/PKD2 activation play a major role in P.
gingivalis LPS-induced up-regulation in salivary gland acinar cell MMP-9
secretion, and point the modulatory mode of action by ghrelin.